U 61 Unsymmetrical trifluoromethyl methoxyphenyl β-diketones: effect of the position of methoxy group and coordination at Cu(II) on biological activity / L. A. Khamidullina, I. S. Puzyrev, P. A. Slepukhin [et al.] // Molecules. - 2021. - Vol. 26, № 21. - Ст. 6466 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): COPPER(II) -- DIKETONATES -- CYTOTOXIC ACTIVITY -- ANTIMICROBIAL ACTIVITY Аннотация: Copper(II) complexes with 1,1,1-trifluoro-4-(4-methoxyphenyl)butan-2,4-dione (HL1) were synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single crystal X-ray diffraction. The biological properties of HL1 and cis-[Cu(L1)2(DMSO)] (3) were examined against Gram-positive and Gram-negative bacteria and opportunistic unicellular fungi. The cytotoxicity was estimated towards the HeLa and Vero cell lines. Complex 3 demonstrated antibacterial activity towards S. aureus comparable to that of streptomycin, lower antifungal activity than the ligand HL1 and moderate cytotoxicity. The bioactivity was compared with the activity of compounds of similar structures. The effect of changing the position of the methoxy group at the aromatic ring in the ligand moiety of the complexes on their antimicrobial and cytotoxic activity was explored. We propose that complex 3 has lower bioavailability and reduced bioactivity than expected due to strong intermolecular contacts. In addition, molecular docking studies provided theoretical information on the interactions of tested compounds with ribonucleotide reductase subunit R2, as well as the chaperones Hsp70 and Hsp90, which are important biomolecular targets for antitumor and antimicrobial drug search and design. The obtained results revealed that the complexes displayed enhanced affinity over organic ligands. Taken together, the copper(II) complexes with the trifluoromethyl methoxyphenyl-substituted β-diketones could be considered as promising anticancer agents with antibacterial properties |
Synthesis and approbation of new neuroprotective chemicals of pyrrolyl- and indolylazine classes in a cell model of Alzheimer's disease / E. A. Dutysheva, I. A. Utepova, M. A. Trestsova [et al.] // European journal of medicinal chemistry. - 2021. - Vol. 222. - P113577 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): PYRROLYLAZINES -- NEUROPROTECTORS -- CHAPERONES -- AMYLOID-BETA -- ALZHEIMER'S DISEASE Аннотация: One of the major causes of neurodegeneration in the pathogenesis of Alzheimer's disease is the accumulation of cytotoxic amyloid species within the intercellular compartments of the brain. The efficacy of the anti-proteotoxic mechanism based on the molecular chaperones Hsp70 and Hsp90 in numerous types of neurons is often low, while its pharmacological enhancement has been shown to ameliorate the physiological and cognitive functions of the brain. Suggesting that the chemicals able to induce heat shock protein synthesis and therefore rescue neural cells from cytotoxicity associated with amyloid, we have synthesized a group of pyrrolyl- and indolylazines that cause the accumulation of heat shock proteins, using a novel method of photocatalysis that is employed in green chemistry. The selected compounds were tested in a cell model of Alzheimer's disease and demonstrated a pronounced neuroprotective effect. These substances increased the survival of neurons, blocked the activation of β-galactosidase, and prevented apoptosis in neurons cultured in the presence of β-amyloid. |